A novel functional CT contrast agent for molecular imaging of cancer

Abstract

The purpose of this study was to investigate the feasibility of using a 2-deoxy-d-glucose (2-DG) labeled gold nanoparticle (AuNP-2-DG) as a functionally targeted computed tomography (CT) contrast agent to obtain high-resolution metabolic and anatomic information of tumor in a single CT scan. Gold nanoparticles (AuNPs) were fabricated and were conjugated with 1-DG or 2-DG. 1-DG provides an excellent comparison since it is known to interfere with the ability of the glucose transporter to recognize the sugar moiety. The human alveolar epithelial cancer cell line, A-549, was chosen for the in vitro cellular uptake assay. Three groups of cell samples were incubated with the 1-DG or 2-DG labeled AuNP and the unlabeled AuNP. Following the incubation, the cells were washed with sterile phosphate buffered saline to remove the excess AuNPs and spun using a centrifuge. The cell pellets were imaged using a microCT scanner immediately after the centrifugation. Internalization of AuNP-2-DG is verified using transmission electron microscopy imaging. Significant contrast enhancement in the cell samples incubated with the AuNP-2-DG with respect to the cell samples incubated with the unlabeled AuNP and the AuNP-1-DG was observed in multiple CT slices. Results from our in vitro experiments suggest that the AuNP-2-DG may be used as a functional CT contrast agent to provide high-resolution metabolic and anatomic information in a single CT scan. These results justify further in vitro and in vivo experiments to study the feasibility of using the AuNP-2-DG as a functional CT contrast agent in radiation therapy settings.

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

“…Fayad and colleagues (174) reported the use of iodinated nanoparticles for cellular imaging of macrophage infiltration in atherosclerotic plaques in rabbits using MDCT. Also, a number of research groups have recently reported the use of targeted gold nanoparticles (known to induce strong X-ray attenuation) with CT for imaging cancer at the cellular and molecular levels (244,340). For example, one group reported the synthesis and evaluation of CT-compatible gold nanoparticles functionalized with prostate specific membrane antigen (PSMA) RNA aptamers (210).…”

Nanoscale radiation transport and clinical beam modeling for gold nanoparticle dose enhanced radiotherapy (GNPT) using X-rays

“…[23][24][25][26][27][28][29] Similarly, imaging contrast agents result in flux suppression and beam hardening but the changes are gradual and no sharp interface effects are observed. New contrast agents are continually under development [43][44][45] and are of potential use not only in imaging but also in radiotherapy. CERT has been studied by various authors mostly from MC computational and treatment planning standpoints.…”

Depth-resolved analytical model and correction algorithm for photothermal optical coherence tomography

“…Multiple imaging modalities have been developed for in vivo molecular imaging, each on different field-of-view and resolution scales, and each with their own advantages and disadvantages. Whole body imaging techniques include magnetic resonance imaging (MRI) [3], computed tomography (CT) [4] and positron emission tomography (PET). These whole body imaging techniques have no limit on imaging depth, but are usually high cost methods, with poor sensitivity to the molecular contrast agent (CT, MRI) and/or involve the use of ionizing radiation (CT, PET).…”